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Abstract Background Chronic pain exerts a significant physical, emotional, and socioeconomic toll on millions of patients worldwide. Traditional pharmacological interventions are often inadequate in providing lasting and effective pain relief for patients suffering from severe chronic pain. However, in recent years, intravenous ketamine infusion therapy has emerged as a promising and alternative treatment modality. The effectiveness of intravenous ketamine infusion therapy in treating chronic pain has been investigated in various pain conditions, such as neuropathic pain, fibromyalgia, complex regional pain syndrome (CRPS), and phantom limb pain. However, varied patient demographics, different endpoints for measuring analgesia, and inconsistent numbers of patients in studies have led to conflicting results. The objective of the present inquiry is to undertake a contemporary updated meta‐analysis of the application of IV ketamine infusion therapy in the context of persistent pain. Methods A search was conducted, adhering to the PRISMA guidelines, to compare the efficacy of IV Ketamine infusion versus control (placebo, midazolam, gabapentin, hydromorphone, and pregabalin) among individuals with chronic pain. During the analysis, Medline, Cochrane, and Embase were thoroughly searched. Two independent investigators identified randomized double‐blind and non‐randomized trials comparing IV Ketamine infusions with controls. Review Manager 5.4.1 was used to scrutinize the data, with the main focus on pain scores. Secondary outcomes such as quality of sleep, as well as side effects such as nausea, hallucinations, and sedation, were also analyzed. Sixteen studies were included involving 1080 patients. Results The pain score was significantly reduced by IV Ketamine (Mean difference −1.05; 95% CI −1.72, −0.39; p = 0.002), while the quality of sleep (Mean difference 0.00; 95% CI −0.12, 0.12; p = 1.00) was not significantly different between studies. Nausea (risk ratio 1.42; 95% CI 0.84, 2.39; p = 0.19), hallucinations (risk ratio 1.08; 95% CI 0.67, 1.76; p = 0.75), and sedation (risk ratio 1.05; 95% CI 0.24, 4.54; p = 0.95) outcomes were not significantly different among the studies. Conclusions Our meta‐analysis indicates that IV Ketamine infusion is efficacious and safe in patients with chronic pain.